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1.
Front Immunol ; 15: 1360296, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38638437

RESUMO

Mast cells have long been recognized for their involvement in allergic pathology through the immunoglobulin E (IgE)-mediated degranulation mechanism. However, there is growing evidence of other "non-canonical" degranulation mechanisms activated by certain pathogen recognition receptors. Mast cells release several mediators, including histamine, cytokines, chemokines, prostaglandins, and leukotrienes, to initiate and enhance inflammation. The chemical nature of activating stimuli influences receptors, triggering mechanisms for the secretion of formed and new synthesized mediators. Mast cells have more than 30 known surface receptors that activate different pathways for direct and indirect activation by microbes. Different bacterial strains stimulate mast cells through various ligands, initiating the innate immune response, which aids in clearing the bacterial burden. Mast cell interactions with adaptative immune cells also play a crucial role in infections. Recent publications revealed another "non-canonical" degranulation mechanism present in tryptase and chymase mast cells in humans and connective tissue mast cells in mice, occurring through the activation of the Mas-related G protein-coupled receptor (MRGPRX2/b2). This receptor represents a new therapeutic target alongside antibiotic therapy. There is an urgent need to reconsider and redefine the biological role of these MASTer cells of innate immunity, extending beyond their involvement in allergic pathology.


Assuntos
Anti-Infecciosos , Hipersensibilidade , Humanos , Animais , Camundongos , Anti-Infecciosos/metabolismo , Citocinas/metabolismo , Imunoglobulina E , Imunidade Inata , Mastócitos , Proteínas do Tecido Nervoso/metabolismo , Receptores de Neuropeptídeos/metabolismo , Receptores Acoplados a Proteínas G/metabolismo
2.
Semin Arthritis Rheum ; 47(1): 38-45, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28259425

RESUMO

OBJECTIVES: To estimate the incidence of severe infection and investigate the associated factors and clinical impact in a large systemic lupus erythematosus (SLE) retrospective cohort. METHODS: All patients in the Spanish Rheumatology Society Lupus Registry (RELESSER) who meet ≥4 ACR-97 SLE criteria were retrospectively investigated for severe infections. Patients with and without infections were compared in terms of SLE severity, damage, comorbidities, and demographic characteristics. A multivariable Cox regression model was built to calculate hazard ratios (HRs) for the first infection. RESULTS: A total of 3658 SLE patients were included: 90% female, median age 32.9 years (DQ 9.7), and mean follow-up (months) 120.2 (±87.6). A total of 705 (19.3%) patients suffered ≥1 severe infection. Total severe infections recorded in these patients numbered 1227. The incidence rate was 29.2 (95% CI: 27.6-30.9) infections per 1000 patient years. Time from first infection to second infection was significantly shorter than time from diagnosis to first infection (p < 0.000). Although respiratory infections were the most common (35.5%), bloodstream infections were the most frequent cause of mortality by infection (42.0%). In the Cox regression analysis, the following were all associated with infection: age at diagnosis (HR = 1.016, 95% CI: 1.009-1.023), Latin-American (Amerindian-Mestizo) ethnicity (HR = 2.151, 95% CI: 1.539-3.005), corticosteroids (≥10mg/day) (HR = 1.271, 95% CI: 1.034-1.561), immunosuppressors (HR = 1.348, 95% CI: 1.079-1.684), hospitalization by SLE (HR = 2.567, 95% CI: 1.905-3.459), Katz severity index (HR = 1.160, 95% CI: 1.105-1.217), SLICC/ACR damage index (HR = 1.069, 95% CI: 1.031-1.108), and smoking (HR = 1.332, 95% CI: 1.121-1.583). Duration of antimalarial use (months) proved protective (HR = 0.998, 95% CI: 0.997-0.999). CONCLUSIONS: Severe infection constitutes a predictor of poor prognosis in SLE patients, is more common in Latin-Americans and is associated with age, previous infection, and smoking. Antimalarials exerted a protective effect.


Assuntos
Corticosteroides/uso terapêutico , Antimaláricos/uso terapêutico , Antirreumáticos/uso terapêutico , Imunossupressores/uso terapêutico , Infecções/epidemiologia , Lúpus Eritematoso Sistêmico/epidemiologia , Adulto , Feminino , Humanos , Incidência , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Masculino , Ácido Micofenólico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença
3.
Medicine (Baltimore) ; 94(1): e267, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25569641

RESUMO

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by multiple organ involvement and pronounced racial and ethnic heterogeneity. The aims of the present work were (1) to describe the cumulative clinical characteristics of those patients included in the Spanish Rheumatology Society SLE Registry (RELESSER), focusing on the differences between patients who fulfilled the 1997 ACR-SLE criteria versus those with less than 4 criteria (hereafter designated as incomplete SLE (iSLE)) and (2) to compare SLE patient characteristics with those documented in other multicentric SLE registries.RELESSER is a multicenter hospital-based registry, with a collection of data from a large, representative sample of adult patients with SLE (1997 ACR criteria) seen at Spanish rheumatology departments. The registry includes demographic data, comprehensive descriptions of clinical manifestations, as well as information about disease activity and severity, cumulative damage, comorbidities, treatments and mortality, using variables with highly standardized definitions.A total of 4.024 SLE patients (91% with ≥4 ACR criteria) were included. Ninety percent were women with a mean age at diagnosis of 35.4 years and a median duration of disease of 11.0 years. As expected, most SLE manifestations were more frequent in SLE patients than in iSLE ones and every one of the ACR criteria was also associated with SLE condition; this was particularly true of malar rash, oral ulcers and renal disorder. The analysis-adjusted by gender, age at diagnosis, and disease duration-revealed that higher disease activity, damage and SLE severity index are associated with SLE [OR: 1.14; 95% CI: 1.08-1.20 (P < 0.001); 1.29; 95% CI: 1.15-1.44 (P < 0.001); and 2.10; 95% CI: 1.83-2.42 (P < 0.001), respectively]. These results support the hypothesis that iSLE behaves as a relative stable and mild disease. SLE patients from the RELESSER register do not appear to differ substantially from other Caucasian populations and although activity [median SELENA-SLEDA: 2 (IQ: 0-4)], damage [median SLICC/ACR/DI: 1 (IQ: 0-2)], and severity [median KATZ index: 2 (IQ: 1-3)] scores were low, 1 of every 4 deaths was due to SLE activity.RELESSER represents the largest European SLE registry established to date, providing comprehensive, reliable and updated information on SLE in the southern European population.


Assuntos
Lúpus Eritematoso Sistêmico/epidemiologia , Sistema de Registros , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Espanha/epidemiologia
4.
Artigo em Espanhol | LILACS | ID: lil-403337

RESUMO

Se realizó un ensayo clínico aleatorio Fase II, controlado a simple ciegas en los pacientes para evaluar la eficacia clínica de un material para impresiones estomatológicas cubano. Fueron realizadas 50 impresiones con el material de ensayo Dentalgín, el cual se le identificó como A y las 50 impresiones restantes fueron realizadas con el material Cromatic, que se denominó B. Con las impresiones realizadas, se construyeron 50 aparatos con el material A y 48 con el material B. En los resultados alcanzados se comprobó, en cuanto a la comparación del grado de homogeneidad de la mezcla de ambos (ensayo y control), que hubo diferencias significativas, así como también fueron notadas en el tiempo de gelificación. En cuanto a los resultados del logro de los principios biomecánicos en la aparatología protésica, construida a partir de las impresiones realizadas con el material A, hubo buen ajuste, retención y estabilidad en 94(por ciento), lo cual se comprobó en la instalación y controles sucesivos. Se calificó el Dentalgín como un material para impresiones estomatológicas eficiente, pues superó la hipótesis formulada de 87


Assuntos
Humanos , Masculino , Adulto , Feminino , Pessoa de Meia-Idade , Alginatos , Materiais para Moldagem Odontológica , Prótese Dentária , Ajuste de Prótese , Ensaios Clínicos Controlados Aleatórios como Assunto
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